Marco Magnoni

Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries: Correlation With Histology and Plaque Echogenicity

OBJECTIVES This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization. BACKGROUND Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies. METHODS Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2). RESULTS In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement. CONCLUSIONS Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

Two Different Mechanisms of Myocardial Ischemia Involving 2 Separate Myocardial Segments in a Patient With Normal Coronary Angiography

A 53-year-old woman with no risk factors was admitted to our hospital in December 2006 because of worsening angina and positive exercise stress test. Two months earlier, she had been admitted to another hospital because of prolonged epigastrial pain without radiation, which had subsided just before she reached the hospital, that was associated with diagnostic elevation of troponin; she reported 3 episodes of the same pain lasting ≈5 minutes in the early morning hours over the preceding 3 weeks. A few hours after admission, she had a recurrence of pain with ST elevation on the inferior electrocardiogram (ECG) leads that responded to intravenous nitrates. Subsequent angiography failed to show lumen stenosis, irregularities, and thrombus deposition, but ventriculography showed akinesia of the basal inferior wall. The discharge diagnosis was inferior ST-elevation myocardial infarction (creatine kinase-MB peak, 112 U/L; troponin I peak, 9.74 ng/mL) with normal coronary arteries, and she was prescribed aspirin, calcium, antagonists, and β-blockers. She remained symptom free for about a month. Then, during a very stressful period of her life, she began to present with anginal pain during effort, sometimes on emotion. She insisted …

Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries

AIMS Arterial vasa vasorum (VV) are known to be involved in the atherosclerotic process. The aim of the present study was to explore whether ultrasound imaging with contrast agent is able to visualize adventitial VV in human carotid atherosclerosis. METHODS AND RESULTS We studied with standard ultrasound 25 patients with carotid stenosis >50% (ATS group) and 15 patients without carotid artery plaques and an intima-media thickness (IMT) <1.0 mm (CTRL group). All patients underwent contrast ultrasound to evaluate periadventitial VV and B-flow imaging (BFI) modality was used to improve and measure periadventitial flow signal. On contrast-enhanced images, a fast microbubble flow and a homogeneous and linear periadventitial contrast signal using BFI were detectable in the adventitial area in all patients of both groups. Periadventitial signal thickness by BFI was higher in patients with atherosclerosis than in the control group (mean +/- SD: CTRL 0.80+/-0.06 mm; ATS 1.10+/-0.11 mm; P<0.001). Moreover, considering the whole study population, the adventitial signal thickness significantly correlated with IMT values (r=0.88, r(2)=0.77; P<0.0001). CONCLUSION Periadventitial contrast signal was detected in all patients and BFI thickness was higher in patient with carotid atherosclerosis and correlated with IMT.

Markers of Inflammation Associated with Plaque Progression and Instability in Patients with Carotid Atherosclerosis

Atherosclerosis is the focal expression of a systemic disease affecting medium- and large-sized arteries, in which traditional cardiovascular risk factor and immune factors play a key role. It is well accepted that circulating biomarkers, including C-reactive protein and interleukin-6, reliably predict major cardiovascular events, including myocardial infarction or death. However, the relevance of biomarkers of systemic inflammation to atherosclerosis progression in the carotid artery is less established. The large majority of clinical studies focused on the association between biomarkers and subclinical atherosclerosis, that is, carotid intima-media thickening (cIMT), which represents an earlier stage of the disease. The aim of this work is to review inflammatory biomarkers that were associated with a higher atherosclerotic burden, a faster disease progression, and features of plaque instability, such as inflammation or neovascularization, in patients with carotid atherosclerotic plaque, which represents an advanced stage of disease compared with cIMT. The association of biomarkers with the occurrence of cerebrovascular events, secondary to carotid plaque rupture, will also be presented. Currently, the degree of carotid artery stenosis is used to predict the risk of future cerebrovascular events in patients affected by carotid atherosclerosis. However, this strategy appears suboptimal. The identification of suitable biomarkers could provide a useful adjunctive criterion to ensure better risk stratification and optimize management.

Assessment of Takayasu Arteritis Activity by Carotid Contrast-Enhanced Ultrasound

A 35-year-old woman was admitted to our institute with a 5-year history of fatigue and low-grade fever. Six months before admission, she had pain in the neck and in the infrascapular region. On admission, the patients heart rate was 80 bpm, her temperature was 37.3°C, and her blood pressure was 130/70 mm Hg in the right arm and 110/70 mm Hg in the left arm. Examination of the neck revealed no jugular venous distention but disclosed bilateral carotid murmurs. Cardiac examination revealed a regular rate and rhythm with a 3/6 holosystolic murmur audibled at the left sternal border. Lung fields were normal. Abdominal examination findings were normal, except for the presence of a palpable spleen and an abdominal bruit at the umbilical left lumbar region. Laboratory examination revealed hemoglobin, 8.5 g/dL (reference ranges, 12.0 to 15.5 g/dL); leukocytes, 21.7×109/L (3.5 to 10.5×109/L); platelets, 460×109/L (150 to 450×109/L); mean corpuscular volume, 76.0 fL (81.6 to 98.3 fL); erythrocyte sedimentation rate, 120 mm/h (0 to 20 mm/h); and …

Non-invasive molecular imaging of vulnerable atherosclerotic plaques

The growing discoveries coming from clinical and basic research during the past decades have revolutionized our knowledge regarding pathophysiologic mechanisms underlying the atherosclerotic process and its thrombotic complications. The traditional view focusing on the severity of stenosis of atherosclerotic plaque has given way to the evidence that the clinical complications of atherosclerotic vascular disease, particularly the propensity to develop thrombotic complications, are determined mainly by the biological composition of the plaque. This paradigm shift has reinforced the need to move from the sole anatomical assessment toward combined anatomic and functional imaging modalities enabling the molecular and cellular characterization of the disease on top of its structural properties. Together, the progress to identify molecular targets related to plaque vulnerability and the improvement of imaging techniques for the detection of such molecular targets have allowed us to obtain new important pathophysiological information. This might allow better patient stratification for the identification of subjects at high risk to develop premature atherosclerosis who might need an aggressive therapeutic approach. Nuclear techniques, magnetic resonance imaging, computed tomography angiography, and contrast-enhanced ultrasound represent the currently available non-invasive imaging modalities for molecular imaging which can provide different and complementary insights into the biological features of the atherosclerotic process. This clinical review will discuss the evidence and potential translational applications of the individual imaging techniques particularly concerning their ability to detect the main atherosclerotic features related to plaque vulnerability, such as plaque inflammation and intertwined neovascularization.

Non-invasive imaging of vascular inflammation

In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [18F]-fluorodeoxyglucose and the new [11C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels.

Carotid atherosclerosis, silent ischemic brain damage and brain atrophy: A systematic review and meta-analysis

BACKGROUND The widespread use of brain imaging has led to increased recognition of subclinical brain abnormalities, including white matter hyperintensities (WMH) and silent brain infarctions (SBI), which have a vascular origin, and have been associated to a high risk of stroke, disability and dementia. Carotid atherosclerosis (CA) may be causative in the development of WMH, SBI and eventually brain atrophy. Aim of the present systematic review and meta-analysis was to assess the existing evidence linking CA to WMH, SBI and brain atrophy. METHODS The relation between CA and WMH, SBI and brain atrophy was investigated through the systematic search of online databases up to September 2015 and manual searching of references and related citations. Pooled estimates were calculated by random-effects model, using restricted maximum likelihood method with inverse variance weighting method. RESULTS Of the 3536 records identified, fifteen were included in the systematic review and 9 were found to be eligible for the meta-analysis. CA was significantly associated with the presence of WMH (Odds Ratio, OR 1.42, confidence interval, CI 1.22-1.66, p<0.0001) and of SBI (OR 1.89, CI 1.46-2.45, p<0.0001). No meta-analysis could be performed for the relation between CA and brain atrophy due to the lack of suitable studies. CONCLUSIONS CA was found to be associated to WMH and SBI. While no causative association can be inferred from the available data, the presence of carotid plaque may be considered a significant risk factor for subclinical cerebral damage.

Clinical recommendations on Cardiac-CT in 2015: a position paper of the Working Group on Cardiac-CT and Nuclear Cardiology of the Italian Society of Cardiology.

We worked out a position paper on cardiac-computed tomography (CCT) endorsed by the Working Group on CCT and Nuclear Cardiology of the Italian Society of Cardiology. The CCT clinical indications were discussed and formulated according to the following two modalities: a brief paragraph dedicated to each indication, with the description of clinical usefulness of different indications; and each indication was rated by the technical panel for appropriateness, using a score assessing whether the use of CCT for each indication is appropriate, uncertain, or inappropriate. All conventional CCT clinical indications, regarding coronary and noncoronary evaluation, were discussed and rated. Moreover, we wrote specific sections regarding the newest CCT applications, such as stress perfusion computed tomography, noninvasive evaluation of fractional flow reserve, and CCT use in athletes. The present study has the following two main objectives: because the diagnostic performance of coronary computed tomography angiography (CCTA) is strictly dependent on adequate technology and local expertise, we strove to provide clinical recommendations on CCTA that may help Italian physicians involved with this diagnostic tool; and to give an update on new indications of CCTA, such as its use for safely discharging patients with suspected acute coronary syndromes from the emergency department, and latest clinical results that have been made possible by the remarkable technology developments of the scanners.

Need for new non-invasive imaging strategies to identify high-risk asymptomatic patients with carotid stenosis

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